Liver-derived FGF21 Promotes Skeletal Muscle Fiber Transition During Exercise

The composition of skeletal muscle fiber types is one of the key factors determining meat quality in livestock and poultry,while exercise stimulation is an important factor leading to similar transformation of muscle fibers.Studies have found that fibroblast growth factor 21(FGF21)in muscle is an important factor in glycolipid metabolism in muscle,and exercise can significantly stimulate the expression of FGF21 in liver.However,whether liver-derived FGF21 affect skeletal muscle fiber type transformation during exercise is unclear.We use the model of exercise mice to discuss the effect of liver-derived FGF21 on the transformation of muscle fiber type,so as to provide theoretical basis for improving meat quality of livestock and poultry,and to explore practical ideas.The main contents and studies are as follows:(1)This experiment was designed to investigate the effect of aerobic exercise on FGF21 expression.In the experiment,mice were made to run at a speed of 12m/min for one hour by using a small animal treadmill.Skeletal muscle,cardiac muscle,fat and liver of the mice were taken immediately after exercise for relevant molecular detection.The results of Quantitative Real-time PCR showed that the m RNA expression of FGF21 in liver was significantly increased after exercise,while the m RNA expression of FGF21 in adipose,skeletal muscle and heart was slightly lower but have no significant difference in exercise group compared with control group.Western blot results showed that the FGF21 protein only increased significantly in skeletal muscle after exercise in mice,but there was no significant difference in liver,adipose and heart.This suggests that hepatogenic FGF21 may play a role in skeletal muscle during exercise.(2)The experiment aims to explore the effect of FGF21 on skeletal muscle fiber conversion after exercise.We used animal treadmill for eight weeks of continuous aerobic exercise training in mice,and by injecting PPARα inhibitor GW6471 to regulate the expression of FGF21 in the liver.The Quantitative Real-time PCR and Western blot results showed that the expression of My HCI,My HCIIa and My HCIIx m RNA in skeletal muscle of mice was increased after exercise.After inhibiting FGF21 expression,the gene transcription and protein expression of oxidized muscle fibers My HCI and My HCIIa were decreased significantly compared with the exercise group,while the gene transcription and protein expression of fermented muscle fibers My HCIIb was increased after GW6471 action.It indicates that hepatogenic FGF21 play a role in the type transformation of skeletal muscle fiber type during exercise,it turns skeletal muscle from fast muscle fiber to slow muscle fiber.(3)To investigate the specific signaling mechanism affecting skeletal muscle fiber conversion,mice were given intraperitoneal injection of p38 MAPK phosphorylation inhibitor SB203580 during continuous aerobic exercise training.The Quantitative Real-time PCR and Western blot results showed that the phosphorylation of p38 MAPK was increased by exercise stimulation,and the expression of exercise-induced My HCI,My HCIIa was reversed after the phosphorylation was inhibited,indicating that phosphorylation of p38 MAPK promotes the transformation of slow muscle fibers in skeletal muscle.In summary,the results of this study showed that FGF21 expression and the phosphorylation of p38 MAPK are involved in the exercise-induced myofibril type transformation process.